The present invention relates to microfluidic devices and the control of fluid flow within those devices. These devices are useful in various biological and chemical systems, as well as in combination with other liquid-distribution devices.
There has been a growing interest in the manufacture and use of microfluidic systems for the acquisition of chemical and biological information. In particular, microfluidic systems allow complicated biochemical reactions to be carried out using very small volumes of liquid. These miniaturized systems exhibit improve response time of reactions, minimize sample volume, and lower reagent usage.
Traditionally, these microfluidic systems have been constructed in a planar fashion using silicon fabrication industry techniques. Representative systems are described, for example, in some early work by Manz et al. (Trends in Anal. Chem. (1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66). These publications show microfluidic devices constructed using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. A cover plate is bonded to the top of the devices to provide closure.
More recently, a number of methods have been developed that allow microfluidic devices to be constructed from plastic, silicone or other polymeric materials. In one such method, a negative mold is first constructed, and plastic or silicone is then poured into or over the mold. The mold can be constructed using a silicon wafer (see, e.g., Duffy et al., Analytical Chemistry (1998) 70: 4974-4984; McCormick et al., Analytical Chemistry (1997) 69: 2626-2630), or by building a traditional injection molding cavity for plastic devices. Some molding facilities have developed techniques to construct extremely small molds. Components constructed using a lithography, electroplating and molding (LIGA) technique have been developed at the Karolsruhe Nuclear Research center in Germany (see, e.g., Schomburg et al., Journal of Micromechanical Microengineering (1994) 4:186-191), and commercialized by MicroParts (Dortmund, Germany). Jenoptik (Jena, Germany) also uses LIGA and a hot-embossing technique. Imprinting methods in PMMA also have been demonstrated (see, Martynova et al., Analytical Chemistry (1997) 69: 4783-4789). However, these techniques do not lend themselves to rapid prototyping and manufacturing flexibility. Additionally, these techniques are limited to planar structures. Moreover, the tool-up costs for both of these techniques are quite high and can be cost-prohibitive.
Traditionally, fluid manipulation in these fluidic systems is controlled by electrokinetic and/or electrophoretic transport. These techniques involve the use of voltages and currents to control fluidic movement. Electrodes are placed within the channels and sufficient voltage is applied to cause the hydrolysis of water within the device. This hydrolysis produces a charge gradient throughout the channels that causes either fluid to flow, or molecules within the fluid to move. These techniques have numerous problems including, but not limited to, the need for metallic electrodes within the chambers, connection of these electrodes to an outside voltage/current source, and the need for this source. Additionally, the hydrolysis of water often causes the formation of bubbles and radicals, which may have adverse effects on the devices or reactions occurring within the device.
Accordingly, there is a need for microfluidic devices capable of controlled fluid transport without requiring the use of current and voltage.
The present invention provides microfluidic devices that can control fluid flow. In one embodiment, such microfluidic devices can be rapidly prototyped with minimal tool-up costs, can be easily manufactured at low cost, and are robust.
The microfluidic devices contain fluidic impedances that can control fluid flow. The devices can accommodate the use of a vast array of liquid reagents or solutions including, but not limited to, aqueous solutions and organic solutions. The microfluidic devices of the present invention can be constructed using a variety of manufacturing techniques.
In one embodiment, a device consists of two or more microfluidic channels that are located on different layers of a three dimensional device. The channels are overlapped in certain areas in order to create fluidic impedances. Fluidic impedances hinder fluid flow through the device. The shape and the amount of overlap in the impedances can be controlled in order to alter the differential pressure necessary to cause fluid to flow through the impedances. In a preferred embodiment, a microfluidic device is formed from stencil layers through which channels have been cut, and the layered stencils are held together with adhesives.
In other embodiments, microfluidic impedances can be incorporated into devices constructed using other techniques. In one embodiment, microfluidic impedances are designed into a solid microfluidic device that is constructed using molding technology. In other embodiments, microfluidic impedances are incorporated into devices constructed using etching techniques usually associated with semiconductor processing. These devices can be constructed from etched silicon, glass, or other materials. Microfluidic impedances can be incorporated into devices constructed using still other techniques as well.
In certain embodiments, a microfluidic device contains one or more of these fluidic impedances. In certain embodiments, all of the fluidic impedances are substantially identical. In other embodiments, the impedances differ within a single device.
The term xe2x80x9cchannelxe2x80x9d as used herein is to be interpreted in a broad sense. Thus, it is not intended to be restricted to elongated configurations where the transverse or longitudinal dimension greatly exceeds the diameter or cross-sectional dimension. Rather, the term xe2x80x9cchannelxe2x80x9d is meant to comprise cavities or tunnels of any desired shape or configuration through which liquids may be directed. Such a fluid cavity may, for example, comprise a flow-through cell where fluid is to be continually passed or, alternatively, a chamber for holding a specified, discrete amount of fluid for a specified amount of time. xe2x80x9cChannelsxe2x80x9d may be filled with a material that allows fluid flow through the channel, or may contain internal structures comprising valves or equivalent components. A channel as used herein typically has a smallest dimension that is at least about 1 micron but is less than about 500 microns.
The term xe2x80x9cmicrofluidicxe2x80x9d as used herein is to be understood to refer to structures or devices through which a fluid is capable of being passed or directed, wherein one or more of the dimensions is less than about 500 microns.
The microfluidic devices described herein are xe2x80x9cgenericxe2x80x9d in that they are modular and can be easily reconfigured into or adapted to any design. In addition, these devices are capable of being used with a variety of pumping and valving mechanisms, including pressure, peristaltic pumping, electrokinetic flow, electrophoresis, vacuum and the like. In addition, the microfluidic devices of the present invention are capable of being used in collaboration with optical detection (e.g., fluorescence, phosphorescence, luminescence, absorbance and colorimetry), electrochemical detection, and any of various suitable detection methods. Suitable detection methods will depend on the geometry and composition of the device. The choice of such detection methods will be within the purview of the skilled artisan.
The term xe2x80x9cmicrofluidic impedancexe2x80x9d as used herein is to be understood to refer to a structure within a microfluidic device that hinders fluid flow. These devices are not limited to the particular shapes, geometries and materials provided herein.
The terms xe2x80x9cpositive pressurexe2x80x9d and xe2x80x9cnegative pressurexe2x80x9d as used herein refer to pressures differing from a reference pressure. A preferred reference pressure is atmospheric pressure.